Dose Effects of Co-Exposure to Polycyclic Aromatic Hydrocarbon and Phthalates on Blood-Cell-Based Inflammatory Indices in Children

Evidence surrounded the effect of co-exposure to polycyclic aromatic hydrocarbons (PAHs) and phthalates (PAEs) on blood-cell-based inflammatory indices was largely unknown. We conducted a panel study among 149 children aged 4-12 years with repeated morning urine collecting over 4 consecutive days prior to blood drawing across 3 seasons. We developed a gas chromatography/tandem mass spectrometry method for simultaneous determination of 10 PAHs metabolites (OH-PAHs) and 10 PAEs metabolites (mPAEs) in the urine sample. We employed the linear mixed-effects model to evaluate the independent effects of urinary OH-PAHs and mPAEs on blood-cell-based inflammatory indices over different lag days. Bayesian kernel machine regression (BKMR) and quantile g-computation were used to evaluate the overall effect of OH-PAHs and mPAEs mixture on blood-cell-based inflammatory indices. After multiple adjustments, we found positive dose-response associations of hydroxynaphthalene (∑OHPHE), hydroxyfluorene, hydroxyphenanthrene, summed OH-PAHs, mono-n-butyl phthalate and summed mPAEs with inflammatory indices such as neutrophil count, neutrophil to lymphocyte ratio, platelet-to-lymphocyte ratio, and the systemic immune-inflammation index at lag0. A 1% increase of ∑OHPHE was related to a 0.18% (95%CI: 0.11%, 0.25%) increment in the systemic immune-inflammation index, which was the strongest among the above associations. Results of Bayesian kernel machine regression (BKMR) and quantile g-computation suggested that co-exposure to OH-PAHs and mPAEs mixture was associated with elevated white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index to which ∑OHPHE and 1-hydroxypyrene (1-OHPYR) might be the major contributors. Besides, gender and age modified the associations of ∑OHPHE and 1-OHPYR with inflammatory indices where girls and younger children might be more susceptible. Totally, OH-PAHs and mPAEs were dose-responsively associated with elevated inflammation in children, in which ∑OHPHE and 1-OHPYR might play important roles.Funding: This work was supported by the National Key Research and Development Program of China (2016YFC0206505).Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Ethics Approval Statement: This study was approved by the Medical Research Ethics Committee of Tongji Medical College, Huazhong University of Science and technology. Informed consent was obtained from all individuals before the study. The consent statement was signed by the child' legal guardian at enrollment.